Th proposed investigation is a correlated ultrastructural and cytochemical approach to the study of retinal degeneration at the subcellular level. It is focused on the photoreceptor-pigmented epithelial cell system and utilizes both in vivo and in vitro methods. The study is based on 1. the application of simple, reliable cytochemical staining methods for localizing enzyme activities at the electron microscope level that have proven useful in various areas of basic science and 2. the availability of two inbred strains of rats, the Royal College of Surgeons (RCS) and the Wag/Rij strains, each of which exhibits characteristic heritable retinal degeneration. The procedures to be used include, in vitro phagocytosis of outer segment material by pigmented epithelial cells, study of lectin-receptor sites on cell surfaces, detection of microtubules and microfilaments, study of lysosomes and their role in phagocytosis and study of vascular alterations. The overall objective of these studies is to learn more about the subcellular alterations that are involved in the pathogenesis of the retinal degenerations in the two animal models, with the idea that such information may eventually aid in understandng retinal degeneration in man.